In situ ascending aortic thrombus in a patient with metastatic lung adenocarcinoma and no aortic atherosclerosis or cisplatin exposure: a case report

Background An ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use. Case A 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process. Conclusion To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.


Introduction
An ascending aortic thrombus without structural risk factors, such as aneurysm, dissection, aortitis, trauma, or severe atherosclerosis, is exceedingly rare.There are only a handful of case reports detailing aortic thrombosis in the context of malignant disease, but the majority involve the thoracic or descending abdominal aorta.The few reports that do include the ascending aorta occurred in patients following cisplatin usage, which is associated with a prothrombotic state.We present the first reported case of a patient who developed an in situ ascending aortic thrombus in the setting of lung malignancy who had not undergone chemotherapy and had no previous aortic structural risk factors.

Case presentation
A 60-year-old white female with a 45-pack-year smoking history and history of asthma presented to the emergency department with several weeks of generalized, nonfocal headache, and dizziness.She denied any visual obscurations, nausea, or vomiting.The patient's family history was only notable for maternal and paternal hypertension and type 2 diabetes mellitus, but no hypercoagulable diseases.A magnetic resonance image (MRI) of the brain with and without contrast demonstrated innumerable round, bilateral lesions with peripheral hyperdensity suspicious for metastatic disease with internal hemorrhage but no midline shift (Fig. 1).A contrast-enhanced computed tomography (CT) of the chest revealed a 2.2cm right upper lobe spiculated mass and extensive hilar lymphadenopathy, suggestive of a primary lung malignancy with metastatic adenopathy (Fig. 2).She decided to leave, against medical advice, but agreed to follow-up in the outpatient setting; she was given dexamethasone 4 mg every 6 h to take at home.At 2 weeks later in the pulmonary clinic, immunohistochemistry of samples from the right hilar lymph node obtained via endobronchial ultrasound confirmed thyroid transcription factor-1 (TTF-1) + adenocarcinoma and low positive programed death ligand 1 (PD-L1) at 30% (Fig. 3).Gene amplification unveiled driver mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C and EIF1AZ.These findings all but confirmed stage IV lung adenocarcinoma.During the procedure, the patient became dyspneic and mildly anxious.Her vitals at the time were notable for sinus tachycardia with a heart rate (HR) of 101 bpm and mild hypoxia saturating 93% on room air.She denied any chest pain, pressure, cough, radiating pain to the left upper extremity, jaw pain, back pain, or sense of impending doom.The pulmonary team sent the patient to the emergency department (ED) for further evaluation.In the ED, the patient's symptoms had improved.Her vital signs and physical exam findings were within normal limits.A respiratory pathogen panel, which included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was negative.A CT angiogram of the chest identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch (Fig. 4), but no pulmonary emboli or intrapulmonary right to left shunts were identified.A hypercoagulable workup was negative at both presentation and at 4 week follow-up (Table 1).The patient was promptly heparinized and carefully watched for symptoms of stroke, limb, or abdominal ischemia.A transthoracic echocardiogram with Definity contrast enhancement noted an left ventricular ejection fraction (LVEF) of 65%, but failed to show an LV thrombus, areas of LV akinesis or hypokinesis, left atrium (LA) dilation, or any atrial septal defects (ASDs), ventricular septal defects (VSDs), or patent foramen ovale (PFO) via agitated saline.An ultrasound of the Fig. 1 Magnetic resonance image brain axial slices at the level of the hypothalamus demonstrating innumerable round, bilateral lesions consistent with florid metastatic spread.A T1-weighted without contrast.B T1-weighted with contrast.C T2-fluid attenuated inversion recovery imaging demonstrating vasogenic edema of occipital lesions lower extremities was similarly negative for deep vein thrombosis.Given the considerable procedural risk and skepticism about recurrence, surgical thrombectomy was deferred.The patient was transitioned to 1 mg/kg twice daily enoxaparin dosing.She remains asymptomatic and a repeat CT of her chest to gauge resolution is in process.She has undergone 2 weeks of whole brain radiation therapy and is pending initiation chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab.
IgG immunoglobulin G, IgM immunoglobulin M, PT prothrombin time, INR international normalized ratio, PTT partial thromboplastin time

Discussion
It is well understood that malignancy can promote a state of hypercoagulability through an increase in procoagulant mucins and tissue factor along with the release of prothrombotic cytokines.An in situ ascending aortic thrombus in the absence of aortic substrate (i.e., dissection, aneurysm, trauma, aortitis, or aortic atherosclerosis) is an extremely rare occurrence, since high laminar flow within this area precludes hemostasis.In this case, the patient had no personal history nor family history of hypercoagulability.Moreover, she had a comprehensive hypercoagulable panel both on presentation and on follow-up, which was negative.As such, evidence points to her florid metastatic spread as the most compelling driver for her aortic thrombosis.
There are only a handful of case reports that detail aortic thrombosis due to hypercoagulability of malignancy [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], and within these studies, the majority have occurred in the descending thoracic or abdominal aorta following viscous energy dissipation, and only four cases involve the ascending aorta (Table 2).Of the four cases, two involved primary bronchogenic carcinomas, and both patients had undergone cisplatin chemotherapy, which is believed to promote a prothrombotic state from elevation of von Willebrand factor levels, hypomagnesemia-associated vasospasm, and LV dysfunction [18].Optimal management for an aortic thrombus and malignant disease is not well established.Several studies support a conservative approach given periprocedural complications, risk for embolism with thrombus manipulation, and poor overall prognosis.In this case, our surgical team deferred intervention for similar reasons.However, it is reasonable to pursue an urgent salvage surgery to rescue ischemic limbs and visceral organs.

Conclusion
To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities.Optimal management for an aortic thrombus and malignant disease is less clear.Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.

Fig. 2 Fig. 3
Fig. 2 Axial (A) and coronal (B) slices of the initial contrast-enhanced chest computed tomography demonstrating a 2.2 × 2.0 cm right upper lobe nodule (blue circle and yellow arrow) with distal scattered nodular opacities

Fig. 4 A
Fig. 4 A and B Coronal and axial sections of the initial contrast enhanced computed tomography of the chest, respectively (from Fig. 2), failing to demonstrate aortic pathology, including dissection or aneurysm.There is calcification noted at the ostia of the left common carotid and left subclavian, but negligent atherosclerosis in the ascending aorta.C and D Comparison of coronal and axial slices, respectively, this time from a computed tomography angiogram of the chest, demonstrating the new aortic thrombus proximal to the aortic arch

Table 1
Full hypercoagulable workup panel demonstrating that all values are within normal limits, suggesting that the ascending aortic thrombus was most likely due to hypercoagulability of malignancy

Table 2
Summary of published reports detailing aortic thromboses stratified by anatomic location in patients with underlying malignancy